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EXPERIMENT INFORMATION

High LET Radiation Induced Carcinogenesis: Epigenetic Mechanisms in Mouse Models of Human Cancers (NNX12AE79G)
Principal Investigator
Research Area:
Radiation health
Species Studied
Scientific Name: Species: Cells, human
Scientific Name: Mus musculus Species: Mouse

Description
OBJECTIVES:
This is a collaborative project with other NASA investigators who are characterizing mouse models of human lung and colon cancers. Data from both the investigator’s laboratory and the literature suggest that epigenetics play a significant role in carcinogenic processes. By describing the changes in DNA methylation and miR regulation of gene expression for these mice, investigators will provide NASA with mechanistic data regarding carcinogenic initiation and progression. By using normal, cancer, and metastatic cancer cell lines they will obtain information regarding epigenetic changes that occur during carcinogenesis based on stage. For example, loss of control of gene expression for extracellular matrix (ECM) remodeling genes may foster metastatic behavior in colon cancer. For this reason they aim to include ECM gene promoter DNA methylation and gene expression among the loci evaluated in this study to the hypothesis that dis-regulation of epigenetic marks and gene expression changes with disease progression. Similarly, the work of other NASA investigators suggests that they will see epigenetically regulated differences among cell lines in expression of inflammatory response pathway gene regulation among lung cell lines. These experiments will provide information regarding radiation responses of these mouse tissues and human cell lines based on the LET of the radiation used. Abnormal epigenetic silencing of genes can occur at a variety of times during tumor progression. If so, does radiation exposure push normal cells to a cancer phenotype and cancer cells to a metastatic phenotype? This question is of importance to NASA since astronauts are of an age where they likely go into missions with precursor lesions. It is important to understand whether their occupational radiation exposures lead to increased cancer risk.

This study had the following specific aims:

  1. Evaluate normal and cancer cell lines from lung and colon for responses to low dose high LET radiation exposure.
  2. Establish epigenetic profiles for in vivo radiation induced cancers in mouse models of human lung and colon cancers.


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Keywords
Cancer
Cell lines
DNA damage
Gene expression
Lung
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Data Information
Data Availability
Archive is complete. Data sets are not publicly available but can be requested.
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Parameters
DNA damage
DNA methylation
Extracellular matrix remodeling genes
Radiation exposure

Mission/Study Information
Mission Launch/Start Date Landing/End Date Duration
Ground 05/01/2009 In Progress

Additional Information
Managing NASA Center
Johnson Space Center (JSC)
Responsible NASA Representative
Johnson Space Center LSDA Office
Project Manager: Terry Hill
Institutional Support
National Aeronautics and Space Administration (NASA)
Proposal Date
03/26/2012
Proposal Source
2011 Space Radiobiology NNJ11ZSA001N